|CRDAMC Homepage | CRDAMC Library Phone #: (254) 288-8366 | CRDAMC Library Fax #: (254) 288-8368|
The soybean has been prized for centuries in Asia as a nutritious, high-protein food with a myriad of uses, and today it's popular in the United States not only in Asian food, but also as a cholesterol-free meat and dairy substitute in traditional American foods. Soy burgers, soy yogurt, tofu hot dogs, and tofu cheese can be found in a growing number of grocery stores alongside the traditional white blocks of tofu, and soy is increasingly used as a protein filler in many prepared foods, including fast-food “hamburger.”
Soy appears to reduce blood cholesterol levels, and the US Food and Drug Administration has authorized allowing foods containing soy to carry a "heart-healthy" label.
Soybeans contain isoflavones, chemicals that are similar to estrogen. These are widely thought to be the active ingredients in soy, although, as discussed below, there is substantial evidence that other constituents may be equally or more important. Much of the information in this article overlaps with that in the Isoflavone article.
If you like Japanese, Chinese, Thai, or Vietnamese food, it's easy to get a healthy dose of soy. Tofu is one of the world's most versatile foods. It can be stir-fried, steamed, or added to soup. You can also mash a cake of tofu and use it in place of ricotta cheese in your lasagna. If you don't like tofu, there are many other soy products to try: plain soybeans, soy cheese, soy burgers, soy milk, or tempeh. Or, you can use a soy supplement instead.
Therapeutic Dosages TOP
The FDA allows soy foods containing 6-½ grams of soy to carry a heart-healthy label. Evidence suggests that a daily intake of 25 g of soy protein is adequate to noticeably reduce cholesterol. This amount is typically found in about 2-½ cups of soy milk or ½ pound of tofu.
Note: Soy is increasingly added to foods in the US as a protein filler, and there are concerns that some people here may be greatly exceeding the amount of soy eaten anywhere else in the world. Even the 25 g amount recommended for reducing cholesterol levels is relatively high. For comparison, in Asia, the average intake of soy is only about 10 g daily.71
Therapeutic Uses TOP
According to the combined evidence of numerous controlled studies, soy can reduce blood cholesterol levels and improve the ratio of LDL ("bad") versus HDL ("good") cholesterol.1,122,136 At an average dosage of 47 g daily, total cholesterol falls by about 9%, LDL cholesterol by 13%, and triglycerides by 10%. Soy's effects on HDL cholesterol itself are less impressive. There is inconsistent evidence regarding whether soy might help reduce high blood pressure.117, 124 Indeed, a comprehensive and careful review of studies investigating the influence of phytoestrogens (including soy meals) on blood pressure found no meaningful effect.140 However, another review found that soy protein (as opposed to other soy products) could significantly reduce blood pressure.143
Soy may reduce the common menopausal symptom known as "hot flashes," but study results conflict.71,125 Soy has not been found helpful for improving the hot flashes that often occur in breast cancer survivors.69,84
Unlike estrogen, soy appears to reduce the risk of uterine cancer.4 Its effect on breast cancer is not as well established, but there are reasons to believe that soy can help reduce breast cancer risk as well,5-7 possibly by reducing estrogen levels and lengthening the menstrual cycle.70 (For more information, see the Isoflavone article.) Soy has shown inconsistent promise for helping to prevent prostate and colon cancers.10-12,118
Soy may be beneficial in diabetes. A soy extract, pinitol, may improve blood sugar control in diabetics.115 And, in addition to its favorable effects on cholesterol, the long-term consumption of a diet rich in soy may reduce blood sugar and improve kidney function in diabetic patients with renal dysfunction.137
Yet another soy extract, pinitol, may improve blood sugar control in people with diabetes.115
A very small study found hints that soy isoflavones might help reduce buildup of abdominal fat.126
What Is the Scientific Evidence for Soy? TOP
Numerous controlled studies indicate that soy can reduce LDL (“bad”) cholesterol by about 10%, and perhaps slightly raise HDL (“good”) cholesterol as well.23,71,87,119,122,136,137,143,144
It has often been assumed that isoflavones are the active ingredients in soy responsible for improving cholesterol profile. However, studies that used purified isoflavones (as opposed to whole soy, or soy protein) have generally failed to find benefit.96,145 It is possible that non-isoflavone constituents of soy, such as proteins, fiber, and phospholipids, may be equally or perhaps even more important than the isoflavones in soy.71,97 In a careful review of 30 studies involving almost 3,000 subjects, researchers determined that isolated soy protein (in the range of 15-40 g per day) modestly reduced LDL cholesterol levels by an average of 6%.142 In another study involving two soy milk products, one made from whole soy beans and the other from isolated soy proteins, researchers found that both were more effective than cow’s milk at reducing LDL cholesterol levels.136 In addition, the substance pinitol appears to have cholesterol-lowering properties.115
However, there are other possibilities as well. One study suggests that the isoflavone daidzein may be only effective for reducing cholesterol when it is converted by intestinal bacterial into a substance called equol.98 It appears that only about one-third of people have the right intestinal bacteria to make equol.
Another study found that soy products may at times have an unusual isoflavone profile—containing high levels of the isoflavone glycitein rather than the more usual genistein and daidzein.67 Glycitein could be inactive regarding cholesterol reduction; in other words, variations in the proportions of specific isoflavone constituents might have made some studied soy isoflavone products inactive.
It has also been suggested that soy protein must be kept in its original state to be effective. Ordinary soy protein extracts are somewhat damaged (“denatured”). In a double-blind study of 120 people, a special soy protein extract—in which the proteins were protected from damage—proved more effective for improving cholesterol profile than did standard denatured soy protein extracts.135
There are other theories, as well. For more information, see the Isoflavone article.
Menopausal Symptoms ("Hot Flashes")
Although study results are not entirely consistent, soy may be helpful for symptoms of menopause, especially "hot flashes." For example, a double-blind, placebo-controlled study involving 104 women found that isoflavone-rich soy protein provided significant relief of hot flashes compared to placebo (milk protein). Improvements in hot flashes, as well as other symptoms such as vaginal dryness, were seen in several other studies of soy or soy isoflavones as well.3,31,32,83,88-90,125,99-101,116 A review of 13 randomized trials with 1,996 women showed a reduced frequency of hot flashes with soy isoflavones compared to placebo, with more than 12 weeks of treatment showing the greatest effect. Hot flash severity improved in 9 randomized trials involving 988 women with soy isoflavones compared to placebo.146 However, about as many studies have failed to find benefit with soy or concentrated isoflavones.34-36,68,71,92,102,120 Furthermore, in three double-blind, placebo-controlled trials, isoflavone-rich soy failed to reduce hot flashes among survivors of breast cancer.69,84,103
To make matters even more complicated, a double-blind study of 241 women experiencing hot flashes found equivalent benefits whether isoflavone-free or isoflavone-rich soy products were used.93
The high rate of the placebo effect seen in many studies of menopausal symptoms may account for these discrepancies. In addition, it is possible that certain formulations of soy contain as yet unidentified ingredients beyond isoflavones that play an important role.
At least two studies found that people who are equol producers (see previous section) may experience greater benefits.138,139
In one study that evaluated the benefits of soy in osteoporosis, a total of 66 postmenopausal women took either placebo (soy protein with isoflavones removed) or soy protein with 56 mg or 90 mg of isoflavones daily for 6 months.37 The group that took the higher dosage of isoflavones showed significant gains in spinal bone density. There was little change in the placebo or low-dose isoflavone groups. This study suggests that the soy isoflavones in soy protein may be effective for osteoporosis.
Very nearly the same results were also seen in a similar study. This 24-week, double-blind study of 69 postmenopausal women found that soy can significantly reduce bone loss from the spine.38
Similar benefits with soy or soy isoflavones have been seen in other human and animal trials; however, other studies have failed to find benefit.39-48,71,85,104-109,123 On balance it is probably fair to say that isoflavones (either as soy, purified isoflavones, or tofu extract) are likely to have a modestly beneficial effect on bone density at most.
Interestingly, one small but long-term study suggests that progesterone cream (another treatment proposed for use in preventing or treating osteoporosis) may decrease the bone-sparing effect of soy isoflavones.110
Estrogen and most other medications for osteoporosis work by fighting bone breakdown. It has been hypothesized that soy may also work in other ways, by helping to increase new bone formation.49,50
Safety Issues TOP
Studies in animals have found soy essentially nontoxic.51 And it is reassuring to note that researchers found no evidence of ill effects when they gave healthy postmenopausal women 900 mg of soy isoflavones a day for 84 consecutive days.141 However, soy or its isoflavones could conceivably have some potentially harmful effects in certain specific situations.
Soy appears to have numerous potential effects involving the thyroid gland. When given to individuals with impaired thyroid function, soy products have been observed to reduce absorption of thyroid medication.58-72 In addition, some evidence hints that soy isoflavones may directly inhibit the function of the thyroid gland, although this inhibition may only be significant in individuals who are deficient in iodine.73,74,111 However, to make matters even more confusing, studies of healthy humans and animals given soy isoflavones or other soy products have generally found that soy either had no effect on thyroid hormone levels or actually increased levels.65,74-78 The bottom line: In view of soy’s complex effects regarding the thyroid, individuals with impaired thyroid function should not take large amounts of soy products except under the supervision of a physician.
Soy may reduce the absorption of the nutrients zinc, iron, and calcium.60-64 To avoid absorption problems, you should probably take these minerals at least 2 hours apart from eating soy.
Other concerns relate to the estrogenic properties of soy isoflavones. For example, while soy is thought to reduce the risk of developing breast cancer, it is possible that soy might not be safe for women who have already had breast cancer. In addition, there are concerns that intensive use of soy products by pregnant women could exert a hormonal effect that impacts unborn fetuses. Finally, fears have been expressed by some experts that soy might interfere with the action of oral contraceptives. However, one study of 36 women found reassuring results.55 For more information on these and other safety issues regarding the isoflavones in soy, see the full Isoflavones article.
One observational study raised concerns that soy might impair mental function.79 However, observational studies are highly unreliable by nature, and experts do not consider this a serious issue.71 Additionally, a number of studies looking at cognitive improvement have found that soy or soy isoflavones either have no effect on mental function, or perhaps minimally improve it.105, 127-129
References[ + ]
1. Anderson JW, Johnstone BM, Cooke-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med. 1995;333:276-281.
2. Albertazzi P, Pansini F, Bonaccorsi G, et al. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol. 1998;91:6-11.
3. Scambia G, Mango D, Signorile PG, et al. Clinical effects of a standardized soy extract in postmenopausal women: a pilot study. Menopause. 2000;7:105-111.
4. Goodman MT, Wilkins LR, Hankin JH, et al. Association of soy and fiber consumption with the risk of endometrial cancer. Am J Epidemiol. 1997;146:294-306.
5. Messina MJ, Persky V, Setchell KDR, et al. Soy intake and cancer risks: a review of the in vitro and in vivo data. Nutr Cancer. 1994;21:113-131.
6. Barnes S, Peterson TG, Coward L. Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer. J Cell Biochem Suppl. 1995;22:181-187.
7. Ingram D, Sanders K, Kolybaba M, et al. Case-control study of phyto-oestrogens and breast cancer. Lancet. 1997;350:990-994.
8. Nagata C, Kabuto M, Kurisu Y, et al. Decreased serum estradiol concentration associated with high dietary intake of soy products in premenopausal Japanese women. Nutr Cancer. 1997;29:228-223.
9. Nagata C, Naoyoshi T, Shizuyo I, et al. Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women. J Natl Cancer Inst. 1998;90:1830-1835.
10. Adlercreutz H, Mazur W. Phyto-oestrogens and western diseases. Ann Med. 1997;29:95-120.
11. Day NE. Phyto-estrogens and hormonally dependent cancers. Pathol Biol. 1994;42:1090.
12. Barnes S, Peterson TG, Coward L. Rationale for the use of genistein-containing soy matrices in chemoprevention trials for breast and prostate cancer. J Cell Biochem Suppl. 1995;22:181-187.
13. Potter SM, Baum JA, Teng H, et al. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr. 1998;68(suppl):1375S-1379S.
14. Alekel DL, St. Germain A, Peterson CT, et al. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr. 2000;72:844-852.
15. Harrison E, Adjei A, Ameho C, et al. The effect of soybean protein on bone loss in a rat model of postmenopausal osteoporosis. J Nutr Sci Vitaminol (Tokyo). 1998;44:257-268.
16. Fanti O, Faugere MC, Gang Z, et al. Systematic administration of genistein partially prevents bone loss in ovariectomized rats in a nonestrogen-like mechanism [abstract]. Am J Clin Nutr. 1998;68(suppl):1517S-1518S.
17. Arjmandi BH, Alekel L, Hollis BW, et al. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr. 1996;126:161-167.
18. Fanti P, Monier-Faugere MC, Geng Z, et al. The phytoestrogen genistein reduces bone loss in short-term ovariectomized rats. Osteoporos Int. 1998;8:274-281.
19. Anderson JJB, Ambrose WW, Garner SC. Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model. Proc Soc Exp Biol Med. 1998;217:345-350.
20. Malochet S, Picherit C, Horcajada-Molteni MN, et al. Do endurance training and soy isoflavones exhibit additive effects on ovariectomy-induced osteopenia in the rat? [abstract]. J Bone Miner Res. 1999;14(suppl 1):S536.
21. Arjmandi BH, Birnbaum R, Goyal NV, et al. Bone-sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content. Am J Clin Nutr. 1998;68(suppl):1364S-1368S.
22. Anderson JW, Johnstone BM, Cooke-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med. 1995;333:276-281.
23. Baum JA, Teng H, Erdman JW Jr, et al. Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women. Am J Clin Nutr. 1998;68:545-551.
24. Wangen KE, Duncan AM, Xu X, et al. Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. Am J Clin Nutr. 2001;73:225-231.
25. Simons LA, von Konigsmark M, Simons J, et al. Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women. Am J Cardiol. 2000;85:1297-1301.
26. Mackey R, Ekangaki A, Eden JA. The effects of soy protein in women and men with elevated plasma lipids. Biofactors. 2000;12:251-257.
27. Sirtori CR, Gianazza E, Manzoni C, et al. Role of isoflavones in the cholesterol reduction by soy proteins in the clinic [letter]. Am J Clin Nutr. 1997;65:166-167.
28. Dalais F, Teede HJ, Kotsopoulos D, et al. The effects of dietary soy protein containing phytoestrogens on lipids and indices of bone turnover in postmenopausal women. Presented at: 83rd Annual Meeting of the Endocrine Society; June 20-23, 2001; Denver, CO.
29. Anderson JW, Johnstone BM, Cooke-Newell ME. Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med. 1995;333:276-281.
30. Albertazzi P, Pansini F, Bonaccorsi G, et al. The effect of dietary soy supplementation on hot flushes. Obstet Gynecol. 1998;91:6-11.
31. Brzezinski A, Adlercreutz H, Shaoul R, et al. Short-term effects of phytoestrogen-rich diet on postmenopausal women. Menopause. 1997;4:89-94.
32. Scambia G, Mango D, Signorile PG, et al. Clinical effects of a standardized soy extract in postmenopausal women: a pilot study. Menopause. 2000;7:105-111.
33. Washburn S, Burke GL, Morgan T, et al. Effect of soy protein supplementation on serum lipoproteins, blood pressure, and menopausal symptoms in perimenopausal women. Menopause. 1999;6:7-13.
34. St. Germain A, Peterson CT, Robinson JG, et al. Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment. Menopause. 2001;8:17-26.
35. Baber RJ, Templeman C, Morton T, et al. Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric. 1999;2:85-92.
36. Knight DC, Howes JB, Eden JA. The effect of Promensil™, an isoflavone extract, on menopausal symptoms. Climacteric. 1999;2:79-84.
37. Potter SM, Baum JA, Teng H, et al. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr. 1998;68(suppl):1375S-1379S.
38. Alekel DL, St. Germain A, Peterson CT, et al. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr. 2000;72:844-852.
39. Harrison E, Adjei A, Ameho C, et al. The effect of soybean protein on bone loss in a rat model of postmenopausal osteoporosis. J Nutr Sci Vitaminol (Tokyo). 1998;44:257-268.
40. Fanti O, Faugere MC, Gang Z, et al. Systematic administration of genistein partially prevents bone loss in ovariectomized rats in a nonestrogen-like mechanism [abstract]. Am J Clin Nutr. 1998;68(suppl):1517S-1518S.
41. Arjmandi BH, Alekel L, Hollis BW, et al. Dietary soybean protein prevents bone loss in an ovariectomized rat model of osteoporosis. J Nutr. 1996;126:161-167.
42. Fanti P, Monier-Faugere MC, Geng Z, et al. The phytoestrogen genistein reduces bone loss in short-term ovariectomized rats. Osteoporos Int. 1998;8:274-281.
43. Anderson JJB, Ambrose WW, Garner SC. Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model. Proc Soc Exp Biol Med. 1998;217:345-350.
44. Malochet S, Picherit C, Horcajada-Molteni MN, et al. Do endurance training and soy isoflavones exhibit additive effects on ovariectomy-induced osteopenia in the rat? [abstract]. J Bone Miner Res. 1999;14(suppl 1):S536.
45. Arjmandi BH, Birnbaum R, Goyal NV, et al. Bone-sparing effect of soy protein in ovarian hormone-deficient rats is related to its isoflavone content. Am J Clin Nutr. 1998;68(suppl):1364S-1368S.
46. Lees CJ, Ginn TA. Soy protein isolate diet does not prevent increased cortical bone turnover in ovariectomized macaques. Calcif Tissue Int. 1998;62:557-558.
47. Jayo MJ. Dietary soy isoflavones and bone loss: a study in ovariectomized monkeys. J Bone Miner Res. 1996;11:S228.
48. Gallagher JC, Rafferty K, Haynatzka V, et al. The effect of soy protein on bone metabolism [abstract]. J Nutr. 2000;130:666S-669S.
49. Fanti O, Faugere MC, Gang Z, et al. Systematic administration of genistein partially prevents bone loss in ovariectomized rats in a nonestrogen-like mechanism [abstract]. Am J Clin Nutr. 1998;68(suppl):1517S-1518S.
50. Fanti P, Monier-Faugere MC, Geng Z, et al. The phytoestrogen genistein reduces bone loss in short-term ovariectomized rats. Osteoporos Int. 1998;8:274-281.
51. Crowell JA, Levine BS, Page JG, et al. Preclinical safety studies of isoflavones [abstract]. J Nutr. 2000;130(suppl):677S.
52. Petrakis NL, Barnes S, King EB, et al. Stimulatory influence of soy protein isolate on breast secretion in pre- and post-menopausal women. Cancer Epidemiol Biomarkers Prev. 1996;5:785-794.
53. Proceedings and abstracts. 3rd International Symposium on the Role of Soy in Preventing and Treating Chronic Disease.October 31-November 3, 1999. Washington, DC. J Nutr. 2000;130:653S-711S.
54. Hilakivi-Clarke L, Cho E, Onojafe I, et al. Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring. Oncol Rep. 1999;6:1089-1095.
55. Martini MC, Dancisak BB, Haggans CJ, et al. Effects of soy intake on sex hormone metabolism in premenopausal women. Nutr Cancer. 1999;34:133-139.
56. Maskarinec G, Franke AA, Williams AE, et al. The effects of an isoflavone intervention on the reproductive cycle of premenopausal women. Presented at: European Conference on Nutrition & Cancer; June 21-24, 2001; Lyon, France.
57. Divi RL, Chang HC, Doerge DR. Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action. Biochem Pharmacol. 1997;54:1087-1096.
58. Chorazy PA, Himelhoch S, Hopwood NJ, et al. Persistent hypothyroidism in an infant receiving a soy formula: case report and review of the literature. Pediatrics. 1995;96(1 pt 1):148-150.
59. Jabbar MA, Larrea J, Shaw RA. Abnormal thyroid function tests in infants with congenital hypothyroidism: the influence of soy-based formula. J Am Coll Nutr. 1997;16:280-282.
60. Navert B, Sandstrom B. Reduction of the phytate content of bran by leavening in bread and its effect on zinc absorption in man. Br J Nutr. 1985;53:47-53.
61. Hallberg L, Rossander L, Skanberg AB. Phytates and the inhibitory effects of bran on iron absorption in man. Am J Clin Nutr. 1987;45:988-996.
62. Heaney RP, Weaver CM, Fitzsimmons ML. Soybean phytate content: effect on calcium absorption. Am J Clin Nutr. 1991;53:745-747.
63. Vohra P, Gray GA, Kratzer FH. Phytic acid-metal complexes. Proc Soc Exp Biol Med. 1965;120:447-449.
64. Evans GW. Normal and abnormal zinc absorption in man and animals: the tryptophan connection. Nutr Rev. 1980;38:137-141.
65. Persky VW, et al. Effect of soy protein on endogenous hormones in postmenopausal women. Am J Clin Nutr. 2002;75:145-153.
66. Dewell A, Hollenbeck CB, Bruce B. The effects of soy-derived phytoestrogens on serum lipids and lipoproteins in moderately hypercholesterolemic postmenopausal women. J Clin Endocrinol Metab. 2002;87:118-121.
67. Sirtori CR, Bosisio R, Pazzucconi F, et al. Soy milk with a high glycitein content does not reduce low-density lipoprotein cholesterolemia in type II hypercholesterolemic patients. Ann Nutr Metab. 2002;46:88-92.
68. Kotsopoulos D, Dalais FS, Liang YL, et al. The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women. Climacteric. 2000;3:161-167.
69. Van Patten CL, Olivotto IA, Chambers GK, et al. Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, controlled clinical trial. J Clin Oncol. 2002;20:1449-1455.
70. Kumar NB, Cantor A, Allen K, et al. The specific role of isoflavones on estrogen metabolism in premenopausal women. Cancer. 2002;94:1166-1174.
71. Messina M, Gardner C, Barnes S. Gaining insight into the health effects of soy but a long way still to go: commentary on the fourth International Symposium on the Role of Soy in Preventing and Treating Chronic Disease. J Nutr. 2002;132:547S-551S.
72. Bell DS, Ovalle F. Use of soy protein supplement and resultant need for increased dose of levothyroxine. Endocr Pract. 2001;7:193-194.
73. Doerge DR, Sheehan DM. Goitrogenic and estrogenic activity of soy isoflavones. Environ Health Perspect. 2002;110(suppl 3):349-353.
74. Chang HC, Doerge DR. Dietary genistein inactivates rat thyroid peroxidase in vivo without an apparent hypothyroid effect. Toxicol Appl Pharmacol. 2000;168:244-252.
75. Duncan AM, Merz BE, Xu X, et al. Soy isoflavones exert modest hormonal effects in premenopausal women. J Clin Endocrinol Metab. 1999;84:192-197.
76. Balmir F, Staack R, Jeffrey E, et al. An extract of soy flour influences serum cholesterol and thyroid hormones in rats and hamsters. J Nutr. 1996;126:3046-3053.
77. Potter SM, Pertile J, Berber-Jimenez MD Soy protein concentrate and isolated soy protein similarly lower blood serum cholesterol but differently affect thyroid hormones in hamsters. J Nutr. 1996;126:2007-2011.
78. Forsythe WA 3rd. Soy protein, thyroid regulation and cholesterol metabolism. J Nutr. 1995;125(suppl 3):619S-623S.
79. White LR, Petrovitch H, Ross GW, et al. Brain aging and midlife tofu consumption. J Am Coll Nutr. 2000;19:242-255.
80. Howes JB, Sullivan D, Lai N, et al. The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolemia. Atherosclerosis. 2000;152:143-147.
81. Jenkins DJ, Kendall CW, Jackson CJ, et al. Effects of high- and low-isoflavone soyfoods on blood lipids, oxidized LDL, homocysteine, and blood pressure in hyperlipidemic men and women. Am J Clin Nutr. 2002;76:365-372.
82. Nestel PJ, Yamashita T, Sasahara T, et al. Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler Thromb Vasc Biol. 1997;17:3392-3398.
83. Faure ED, Chantre P, Mares P. Effects of a standardized soy extract on hot flushes: a multicenter, double-blind, randomized, placebo-controlled study. Menopause. 2002;9:329-334.
84. Quella SK, Loprinzi CL, Barton DL. Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial. J Clin Oncol. 2000;18:1068-1074.
85. Morabito N, Crisafulli A, Vergara C, et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized, double-blind, placebo-controlled study. J Bone Miner Res. 2002;17:1904-1912.
86. Burke BE, Olson RD, Cusack BJ. Randomized, controlled trial of phytoestrogen in the prophylactic treatment of menstrual migraine. Biomed Pharmacother. 2002;56:283-288.
87. Clarkson TB. Soy, soy phytoestrogens and cardiovascular disease. J Nutr. 2002;132 :566S-569S.
88. Murkies AL, Lombard C, Strauss BJ, et al. Dietary flour supplementation decreases post-menopausal hot flushes: effect of soy and wheat. Maturitas. 1995;21:189-195.
89. Han KK, Soares JM, Haidar MA, et al. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. Obstet Gynecol. 2002;99:389-394.
90. Upmalis DH, Lobo R, Bradley L, et al. Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study. Menopause. 2000;7:236-242.
91. van de Weijer P, Barentsen R. Isoflavones from red clover (Promensil®) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas. 2002;42:187.
92. Penotti M, Fabio E, Modena AB, et al. Effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the pulsatility index of the uterine and cerebral arteries. Fertil Steril. 2003;79:1112-1117.
93. Burke GL, Legault C, Anthony M, et al. Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study. Menopause. 2003;10:147-153.
94. Gardner-Thorpe D, O'Hagen C, Young I, et al. Dietary supplements of soya flour lower serum testosterone concentrations and improve markers of oxidative stress in men. Eur J Clin Nutr. 2003;57:100-106.
95. McFadyen IJ, Chetty U, Setchell KD, et al. A randomized double blind-cross over trial of soya protein for the treatment of cyclical breast pain. Breast. 2000;9:271-276
96. Yeung J, Yu TF. Effects of isoflavones (soy phyto-estrogens) on serum lipids: a meta-analysis of randomized controlled trials. Nutr J. 2003 Nov 19. [Epub ahead of print]
97. Hoie LH, Morgenstern EC, Gruenwald J, et al. A double-blind placebo-controlled clinical trial compares the cholesterol lowering effects of two different soy protein preparations in hypercholesterolemic subjects. Eur J Nutr. 2004 Apr 5. [Epub ahead of print]
98. Meyer BJ, Larkin TA, Owen AJ, et al. Limited lipid-lowering effects of regular consumption of whole soybean foods. Ann Nutr Metab. 2003 Dec 6. [Epub ahead of print]
99. Crisafulli A, Marini H, Bitto A, et al. Effects of genistein on hot flushes in early postmenopausal women: a randomized, double-blind EPT- and placebo-controlled study. Menopause. 2004;11:400-404.
100. Chiechi LM, Putignano G, Guerra V, et al. The effect of a soy rich diet on the vaginal epithelium in postmenopause: a randomized double blind trial. Maturitas. 2003;45:241-246.
101. Messina M, Hughes C. Efficacy of soyfoods and soybean isoflavone supplements for alleviating menopausal symptoms is positively related to initial hot flush frequency. J Med Food. 2003;6:1-11.
102. Penotti M, Fabio E, Modena AB, et al. Effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the pulsatility index of the uterine and cerebral arteries. Fertil Steril. 2003;79:1112-1117
103. Nikander E, Kilkkinen A, Metsa-Heikkila M, et al. A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients. Obstet Gynecol. 2003;101:1213-1220.
104. Dalais FS, Ebeling PR, Kotsopoulos D, et al. The effects of soy protein containing isoflavones on lipids and indices of bone resorption in postmenopausal women. Clin Endocrinol (Oxf). 2003;58:704-709.
105. Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women. JAMA. 2004;292:65-74.
106. Yoles I, Yogev Y, Frenkel Y, et al. Tofupill/Femarelle (DT56a): a new phyto-selective estrogen receptor modulator-like substance for the treatment of postmenopausal bone loss. Menopause. 2003;10:522-525.
107. Chen YM, Ho SC, Lam SS, et al. Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial. J Clin Endocrinol Metab. 2003;88:4740-4747.
108. Cotter A, Cashman KD. Genistein appears to prevent early postmenopausal bone loss as effectively as hormone replacement therapy. Nutr Rev. 2003;61:346-351.
109. Atkinson C, Compston JE, Day NE, et al. The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2004;79:326-333.
110. Lydeking-Olsen E, Beck-Jensen JE, Setchell KD, et al. Soymilk or progesterone for prevention of bone loss. A 2 year randomized, placebo-controlled trial. Eur J Nutr. 2004 Apr 14. [Epub ahead of print]
111. Bruce B, Messina M, Spiller GA. Isoflavone supplements do not affect thyroid function in iodine-replete postmenopausal women. J Med Food. 2003;6:309-316.
112. Arjmandi BH, Khalil DA, Lucas EA, et al. Soy protein may alleviate osteoarthritis symptoms. Phytomedicine. 2005;11:567-575.
113. Kobayashi M, Matsushita H, Shioya I, et al. Quality of life improvement with soy sauce ingredients, Shoyu polysaccharides, in perennial allergic rhinitis: a double-blind placebo-controlled clinical study. Int J Mol Med. 2004;14:885-889.
114. Kobayashi M, Matsushita H, Tsukiyama R, et al. Shoyu polysaccharides from soy sauce improve quality of life for patients with seasonal allergic rhinitis: a double-blind placebo-controlled clinical study. Int J Mol Med. 2005;15:463-467.
115. Kim JI, Kim JC, Kang MJ, et al. Effects of pinitol isolated from soybeans on glycaemic control and cardiovascular risk factors in Korean patients with type II diabetes mellitus: a randomized controlled study. Eur J Clin Nutr 2004 Dec 10. [Epub ahead of print]
116. Kok L, Kreijkamp-Kaspers S, Grobbee DE, et al. A randomized, placebo-controlled trial on the effects of soy protein containing isoflavones on quality of life in postmenopausal women. Menopause. 2005;12:56-62.
117. He J, Gu D, Wu X et al. Effect of soybean protein on blood pressure: a randomized, controlled trial. Ann Intern Med. 2005;143:1-9.
118. Adams KF, Lampe PD, Newton KM, et al. Soy protein containing isoflavones does not decrease colorectal epithelial cell proliferation in a randomized controlled trial. Am J Clin Nutr. 2005;82:620-626.
119. Hoie LH, Graubaum HJ, Harde A, et al. Lipid-lowering effect of 2 dosages of a soy protein supplement in hypercholesterolemia. Adv Ther. 2005;22:175-186.
120. Manonai J, Songchitsomboon S, Chanda K, et al. The effect of a soy-rich diet on urogenital atrophy: A randomized, cross-over trial. Maturitas. 2005 Nov 15. [Epub ahead of print].
121. Cesarone MR, Belcaro G, Nicolaides AN, et al. Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial. Angiology. 2003;54:531-539.
122. Reynolds K, Chin A, Lees KA, et al. A meta-analysis of the effect of soy protein supplementation on serum lipids. Am J Cardiol. 2006;98:633-640.
123. Newton KM, Lacroix AZ, Levy L, et al. Soy protein and bone mineral density in older men and women: A randomized trial. Maturitas 2006 May 24. [Epub ahead of print]
124. Teede HJ, Giannopoulos D, Dalais FS, et al. Randomised, controlled, cross-over trial of soy protein with isoflavones on blood pressure and arterial function in hypertensive subjects. J Am Coll Nutr. 2006;25:533-540.
125. Welty FK, Lee KS, Lew NS, et al. The Association between soy nut consumption and decreased menopausal symptoms. J Womens Health (Larchmt). 2007;16:361-369.
126. Sites CK, Cooper BC, Toth MJ, et al. Effect of a daily supplement of soy protein on body composition and insulin secretion in postmenopausal women. Fertil Steril. 2007 Apr 3. [Epub ahead of print]
127. Fournier LR, Ryan Borchers TA, Robison LM, et al. The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women. J Nutr Health Aging. 2007;11:155-164.
128. Duffy R, Wiseman H, File SE. Improved cognitive function in postmenopausal women after 12 weeks of consumption of a soya extract containing isoflavones. Pharmacol Biochem Behav. 2003;75:721-729.
129. File SE, Hartley DE, Elsabagh S, et al. Cognitive improvement after 6 weeks of soy supplements in postmenopausal women is limited to frontal lobe function. Menopause. 2005;12:193-201.
130. Armstrong WB, Kennedy AR, Wan XS, et al. Clinical modulation of oral leukoplakia and protease activity by Bowman-Birk inhibitor concentrate in a phase IIa chemoprevention trial. Clin Cancer Res. 2000;6:4684-4691.
131. Meyskens FL. Development of Bowman-Birk inhibitor for chemoprevention of oral head and neck cancer. Ann N Y Acad Sci. 2001;952:116-123.
132. Meyskens FL. Development of Bowman-Birk inhibitor for chemoprevention of oral head and neck cancer. Ann N Y Acad Sci. 2001;952:116-123.
133. Armstrong WB, Wan XS, Kennedy AR, et al. Development of the Bowman-Birk inhibitor for oral cancer chemoprevention and analysis of Neu immunohistochemical staining intensity with Bowman-Birk inhibitor concentrate treatment. Laryngoscope. 2003;113:1687-1702.
134. Lichtenstein GR, Deren JJ, Katz S et al. Bowman-Birk Inhibitor concentrate: a novel therapeutic agent for patients with active ulcerative colitis. Dig Dis Sci. 2007 Jun 6. [Epub ahead of print]
135. Hoie LH, Guldstrand M, Sjoholm A, et al. Cholesterol-lowering effects of a new isolated soy protein with high levels of nondenaturated protein in hypercholesterolemic patients. Adv Ther. 2007;24:439-447.
136. Gardner CD, Messina M, Kiazand A, et al. Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial. J Am Coll Nutr. 2007;26:669-677.
137. Azadbakht L, Atabak S, Esmaillzadeh A. Soy protein intake, cardio-renal indices and C-reactive protein in type 2 diabetes with nephropathy: a longitudinal randomized clinical trial. Diabetes Care. 2008 Jan 9.
138. Uesugi S, Watanabe S, Ishiwata N, et al. Effects of isoflavone supplements on bone metabolic markers and climacteric symptoms in Japanese women. Biofactors. 2005;22:221-228.
139. Jou HJ, Wu SC, Chang FW, et al. Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones. Int J Gynaecol Obstet. 2008 Apr 4.
140. Rosero Arenas MA, Rosero Arenas E, Portaceli Arminana MA, et al. Usefulness of phyto-oestrogens in reduction of blood pressure. Systematic review and meta-analysis. Aten Primaria. 2008;40:177-186.
141. Pop EA, Fischer LM, Coan AD, et al. Effects of a high daily dose of soy isoflavones on DNA damage, apoptosis, and estrogenic outcomes in healthy postmenopausal women: a phase I clinical trial. Menopause. 2008 Apr 28.
142. Harland JI, Haffner TA. Systematic review, meta-analysis and regression of randomised controlled trials reporting an association between an intake of circa 25g soya protein per day and blood cholesterol. Atherosclerosis. 2008 Apr 15.
143. Hooper L, Kroon PA, Rimm EB, et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2008;88:38-50.
144. Shidfar F, Ehramphosh E, Heydari I, et al. Effects of soy bean on serum paraoxonase 1 activity and lipoproteins in hyperlipidemic postmenopausal women. Int J Food Sci Nutr. 2008 May 19
145. Thorp AA, Howe PR, Mori TA, et al. Soy food consumption does not lower LDL cholesterol in either equol or nonequol producers. Am J Clin Nutr. 2008;88:298-304.
146. Taku K, Melby MK, Kronenberg F, et al. Extracted or synthesized soybean isoflavones reduce menopausal hot flash frequency and severity: systematic review and meta-analysis of randomized controlled trials. 2012;19(7):776-790.
Last reviewed December 2015 by EBSCO CAM Review Board
Last Updated: 12/15/2015
EBSCO Information Services is fully accredited by URAC. URAC is an independent, nonprofit health care accrediting organization dedicated to promoting health care quality through accreditation, certification and commendation.
This content is reviewed regularly and is updated when new and relevant evidence is made available. This information is neither intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with questions regarding a medical condition.
To send comments or feedback to our Editorial Team regarding the content please email us at firstname.lastname@example.org. Our Health Library Support team will respond to your email request within 2 business days.